Preferred Label : Autologous HLA-A*11:01 KRASG12V-specific TCR-expressing CD8- and CD4-positive T-lymphocytes
AFNT-211;
NCIt synonyms : Autologous FAS-41BB-enhanced HLA-A*11:01 KRASG12V-specific TCR-T Cells AFNT-211; Autologous Engineered TCR T-cells AFNT-211;
NCIt definition : A preparation of autologous HLA class I histocompatibility antigen A*11:01 (HLA-A1101)-positive
CD8- and CD4-positive T-lymphocytes that have been transduced with a lentiviral vector
expressing a HLA-A*11:01-restricted T-cell receptor (TCR) that recognizes the glycine
to valine point mutation at position 12 (G12V) variant of Kirsten rat sarcoma (K-RAS;
KRAS), and enhanced with the wildtype CD8alpha/beta (CD8a/b) coreceptor, and a FAS-41BB
switch receptor, and subsequently expanded ex vivo, with potential immunomodulating
and antineoplastic activities. When reintroduced into the patient, the autologous
HLA-A*11:01 KRASG12V-specific TCR-expressing CD8- and CD4-positive T-lymphocytes AFNT-211
specifically recognize and bind to KRASG12V expressed on tumor cells, which results
in both cytokine secretion and cell lysis in tumor cells overexpressing KRASG12V.
K-RAS, a member of the RAS family of oncogenes, serves an important role in cell signaling,
division and differentiation. The KRASG12V mutation is overexpressed in a variety
of cancer cell types. Mutation of K-RAS may induce constitutive signal transduction
leading to tumor cell growth, proliferation, invasion, and metastasis. CD8a/b coreceptor
and a FAS-41BB switch receptor improve T-cell persistence. The introduction of the
CD8a/b coreceptor enables a coordinated CD4 /CD8 T-cell response and enables CD4
T-cell recognition of KRASG12V and enhances cytotoxicity. FAS-41BB converts the FAS
ligand (FASL) tumor microenvironment (TME) death signal into a costimulatory signal
through 41BB activation, thereby enhancing the durability of the anti-tumor immune
response against FASL-expressing tumor cells.;
Molecule name : AFNT-211; AFNT 211;
NCI Metathesaurus CUI : CL1926985;
Origin ID : C204799;
UMLS CUI : C5908056;
Semantic type(s)
- Cell [UMLS semantic type]
- chemical_or_drug_affects_cell_type_or_tissue
- chemical_or_drug_has_mechanism_of_action
- chemical_or_drug_has_physiologic_effect
- concept_is_in_subset
- has_target
